Isothermal thermodynamic parameters will be determined calorimetrically for transitions between two well-defined conformational states. These transitions will be induced through isomeric substitutions in rigid peptides. The 3 yields 1 hydrogen bond of derivatives of acetyl-L-proline-methylamide and peptide-aromatic interactions in compounds such as cyclo (Pro-Tyr) will be investigated. The corresponding thermal transitions of individual compounds will be characterized by vant Hoff analysis of DC and NMR spectra. In addition, the isothermal thermodynamics of peptide-solvent interactions will be probed in rigid bicyclic lactams derived from proline. Solvent-induced conformational changes will be determined spectroscopically for sterically-hindered peptides derived from alpha-methyl-amino-acid. The role of bulk solvent properties and specific peptide-solvent interactions will be assessed. Conformational distributions will be determined in a variety of solvents for diamides and dipeptides (triamides) of novel sterically-restricted amino acids, including one which will yield only cis peptides. Circular dichroism spectra will be determined for peptides of fixed conformation such as the bicyclic-proline-lactams. NMR spectra of peptides such as cyclo(dehydro-prolyl-glycyl-) in lipid multilayers will be analyzed to give the orientation and structure of the peptide. The above data will be used to refine the experimental determination and theoretical prediction of peptide conformation. Thus the bioactivities of peptides would be correlated reliably with their conformation. Hence, a peptide with a particular activity dictated by its conformation could be designed from the novel amino acids.